A major problem with current AIDS vaccines has been the relatively weak immunogenicity of recombinant envelope gp120. These vaccines elicit neutralizing antibody titers at least 10 to 20-fold lower than those observed during infection. In addition, when tested against fresh isolates, particularly macrophage tropic isolates, virtually no neutralizing antibodies were detected in vaccines. Our goal is to enhance vaccine potency of gp120 by at least 100-fold, while retaining the important structures recognized by broadly reactive neutralizing antibodies. We have made 2 discoveries leading to the present work: first, broadly specific neutralizing antibodies target the conformation- dependent CD4 binding site on gp120. Second, gp120 has an insert acceptor site, where deletions or insertions can be made without losing the.protein conformation. By inserting appropriate carrier protein sequences at this site, we hope to combine the strong immunogenicity of a carrier protein with the antigenicity of native gp120, resulting in a potent HIV-1 vaccine for humans.